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Angiotensin II amplifies macrophage-driven atherosclerosis
Ayabe Nobuhiko1, Eisuke Suganuma, Vladimir R Babaev
1Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tenn, USA.
Arteriosclerosis, Thrombosis, and Vascular Biology
|September 18, 2004
Summary
Angiotensin II (AII) initiates and sustains atherosclerosis by promoting macrophage migration and elastin fragmentation. This study highlights AII
Area of Science:
- Cardiovascular Research
- Immunology
- Endocrinology
Background:
- Atherosclerosis is a chronic inflammatory disease.
- The role of angiotensin II (AII) in atherosclerosis is complex and not fully understood.
- Macrophage-driven inflammation plays a critical role in atherogenesis.
Purpose of the Study:
- To investigate the specific role of angiotensin II (AII) in a mouse model of atherosclerosis driven by marrow-derived macrophages.
- To elucidate the mechanisms by which AII influences atherosclerotic lesion development.
Main Methods:
- Bone marrow transplantation was used to create chimeric mice with either apolipoprotein E-deficient (apoE-/-) or wild-type (apoE+/+) bone marrow.
- Mice were infused with AII or saline for two weeks.
- Atherosclerotic area, macrophage infiltration, elastin fragmentation, and in vitro monocyte migration were assessed.
Main Results:
- Angiotensin II (AII) significantly increased atherosclerotic area by 3-fold in apoE-/- mice compared to saline-treated controls.
- AII treatment did not affect atherosclerosis in wild-type apoE+/+ mice.
- AII increased macrophage infiltration and elastin laminae fragmentation in both apoE-/- and apoE+/+ mice.
- In vitro, AII enhanced monocyte chemoattractant protein-1-stimulated macrophage migration.
Conclusions:
- Angiotensin II (AII) exhibits both initiating and sustaining proatherogenic effects.
- AII promotes atherosclerosis by enhancing macrophage migration into the vascular intima.
- AII may also contribute to atherosclerotic lesion progression by inducing elastin fragmentation, a novel mechanism affecting smooth muscle cell behavior.